Functional consequences of repeated organophosphate exposure: potential non-cholinergic mechanisms.
Functional consequences of repeated organophosphate exposure: potential non-cholinergic mechanisms.
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DOI：
10.1016/j.pharmthera.2012.03.001
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发表时间：
2012-06
影响因子：
13.5
通讯作者：
Terry, A. V., Jr.
中科院分区：
文献类型：
--
作者：
Terry, A. V., Jr.
这类被称为“有机磷”(OPS)的化学物质包括世界各地使用的许多最常见的农业和商业杀虫剂以及剧毒的化学战剂。有机磷农药在靶生物和非靶生物中的急性毒性机制主要归因于对各种形式的胆碱酯酶的抑制作用，导致外周和中枢胆碱能活性过高。然而，现在有大量证据表明，这种典型的(基于胆碱酯酶的)机制不能单独解释已描述的OP暴露的各种不良后果，特别是那些与反复暴露于没有明显急性毒性迹象的水平有关的不良后果。这种类型的暴露与注意力、记忆力和其他认知领域的长期损害以及这些症状表现出来的慢性疾病(例如海湾战争疾病、阿尔茨海默病)有关。由于其高度活性的性质，有机磷农药可能会改变一些酶和蛋白质的功能(除了胆碱酯酶)也就不足为奇了。然而，与OPS相关的各种长期神经精神症状表明，在暴露期间，一些基本或基本的神经元过程受到了不利影响。本文的目的是讨论OPs的几个可能影响这些基本过程的非胆碱酯酶靶点，包括参与轴突运输的细胞骨架和运动蛋白，神经营养素及其受体，以及线粒体(特别是它们在轴突中的形态和运动)。这些OP相互作用的潜在治疗意义也被讨论。
The class of chemicals known as the “organophosphates” (OPs) comprises many of the most common agricultural and commercial pesticides that are used worldwide as well as the highly toxic chemical warfare agents. The mechanism of the acute toxicity of OPs in both target and non-target organisms is primarily attributed to inhibitory actions on various forms of cholinesterase leading to excessive peripheral and central cholinergic activity. However, there is now substantial evidence that this canonical (cholinesterase-based) mechanism cannot alone account for the wide-variety of adverse consequences of OP exposure that have been described, especially those associated with repeated exposures to levels that produce no overt signs of acute toxicity. This type of exposure has been associated with prolonged impairments in attention, memory, and other domains of cognition, as well as chronic illnesses where these symptoms are manifested (e.g., Gulf War Illness, Alzheimer’s disease). Due to their highly reactive nature, it is not surprising that OPs might alter the function of a number of enzymes and proteins (in addition to cholinesterase). However, the wide variety of long-term neuropsychiatric symptoms that have been associated with OPs suggests that some basic or fundamental neuronal process was adversely affected during the exposure period. The purpose of this review is to discuss several non-cholinesterase targets of OPs that might affect such fundamental processes and includes cytoskeletal and motor proteins involved in axonal transport, neurotrophins and their receptors, and mitochondria (especially their morphology and movement in axons). Potential therapeutic implications of these OP interactions are also discussed.
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影响因子：
8.3
作者：
Amr, MM;Halim, ZS;Moussa, SS
通讯作者：
Moussa, SS
DOI：
10.1006/faat.1997.2329
发表时间：
1997-08-01
期刊：
FUNDAMENTAL AND APPLIED TOXICOLOGY
影响因子：
--
作者：
Chanda, SM;Mortensen, SR;Padilla, S
通讯作者：
Padilla, S
影响因子：
1.1
作者：
Burklow, TR;Yu, CE;Madsen, JM
通讯作者：
Madsen, JM
DOI：
10.1016/s0165-3806(00)00021-3
发表时间：
2000-05-11
期刊：
DEVELOPMENTAL BRAIN RESEARCH
影响因子：
--
作者：
Auman, JT;Seidler, FJ;Slotkin, TA
通讯作者：
Slotkin, TA
影响因子：
3.8
作者：
Betancourt, AM;Carr, RL
通讯作者：
Carr, RL